The goal of the YCC Proteomics Shared Resource (PSR) is to bring state-of-the-art technologies to bear on cancer research. These technologies include a wide range of mass spectrometric (MS) approaches to determine accurate molecular weights of proteins, peptides, small synthetic molecules (e.g., anti-cancer drugs), and other biomolecules. MS is also used for high throughput identification of proteins, typically following their enzymatic digestion. These proteins are often selected for identification based on their differential expression in normal versus cancer tissues or in response to chemotherapy. Protein profiling technologies used to interrogate the expression levels of hundreds of proteins include isotope-coded affinity tags (ICAT), differential (fluorescence) gel electrophoresis (DIGE), multiplexed tagging reagent (iTRAQ), and multidimensional protein identification technology (MudPIT). Unless MudPIT is combined with in vivo metabolic stable isotope labeling, its use is restricted to identifying the proteins that make up a given proteome. In each profiling experiment, a control is compared to a cancer or other experimental sample to identify proteins that are highly differentially expressed. Another approach for finding serum peptide biomarkers whose intensities can be used to diagnose cancer relies on methodologies and biostatistical algorithms implemented in the PSR to analyze MS spectra from large numbers of patients. Another PSR goal is to utilize advanced technologies, including the unique capabilities of its state-of-the-art 9.4T FT-ICR mass spectrometer, to identify protein post-translational modifications (PTM) such as phosphorylation, methylation, and others that often play important roles in modulating protein function and may be involved in tumorigenesis. Since the fraction of protein molecules bearing a given PTM is often low, methodologies are being implemented to enrich for proteins containing specific PTMs. Also of great importance to cancer research is the quantitative characterization of molecular interactions between biological molecules including proteins, nucleic acids, carbohydrates, lipids, and small molecules such as anti-cancer drugs. The Biophysics section of the PSR provides YCC investigators with several complementary technologies for: a) identifying the oligomeric state of interacting components, b) determining the stoichiometry of the interaction, and c) quantifying the forces responsible for macromolecular recognition and complex formation. Biophysical technologies available include: static and dynamic light scattering, steady-state and stopped-flow fluorescence and absorbance, isothermal calorimetry and surface plasmon resonance. Overall, 39 peer reviewed YCC investigators from 7 programs accounted for 19.8% of PSR services provided in CY2005.